Natural Pregnancy, Pregnancy, Ovarian
Conditions
Keywords
Genomic imprinting, Reproductive techniques, assisted, Beckwith-Wiedemann syndrome, Angelman syndrome
Brief summary
Genomic imprinting, referring to an epigenetic marking resulting in monoallelic gene expression, plays a critical role in development. Recently, various imprinting diseases were reported in animals (Large Offspring syndrome (LOS)) and humans (Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS)) born after ART. In all cases, an imprinting defect was involved (loss of methylation at ICR2 in BWS, at SNRPN in AS and at IGF2R DMR2 in LOS). These data suggest that ART procedures may impair the establishment or the maintenance (following fertilization) of methylation marks at maternally imprinted loci. In view of these data, the aim of this study is to determine if children born following ART exhibit an increased risk of imprinting defects. If the answer is yes, the second objective is to identify the problematic step in the ART procedure and thus to suppress or modify this step.
Detailed description
Methodology: assessment of the methylation status at 9 different imprinted loci (using Southern blot and methyl-specific quantitative PCR) in 3 groups of patients: 150 children naturally conceived, 150 children conceived after ovarian stimulation but with in vivo fertilization, and 150 children conceived after ovarian stimulation and in VITRO fertilization. These analyses will be performed on cord blood. Fragments of placental tissue will also be collected for further analyses. Patients will be selected in maternity hospitals associated with ART departments ( ANTOINE BECLERE HOSPITAL, Cochin HOSPITAL, Saint-Vincent de Paul HOSPITAL, Jean VERDIER HOSPITAL, Tenon HOSPITAL and Dijon Hospital). This work is also a unique opportunity to establish a DNA, RNA and tissue collection allowing further investigation regarding other epigenetic modifications than DNA methylation, not only at imprinted loci, but also in other genomic regions regulated by epigenetic modifications.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
26 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
Mother : * Age: 26 to 40 at conception * Single foetus pregnancy * Signed informed consent * Affiliation to French health benefits * Absence of maternal pathology * Normal foetal karyotype (if available) * Known procedure of ovarian stimulation * ART procedure without sperm or oocyte donation * ART in a participating ART departments * Delivery in a participating hospital Father * Age : 18 to 50 at conception * Signed informed consent
Exclusion criteria
* Abnormal foetal karyotype (if available) * Delivery before 35 weeks of amenorrhea * Delivery in not participating hospital * Delivery complication leading to the absence of sample collection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth. | At the birth |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci. | At the birth |
Countries
France
Outcome results
None listed